Strength and durability of RSV pre-fusion F IgG following infection and exposure in a household cohort, 2014-2022

Little is known about the strength and durability of protection (CoP) provided by pre-F IgG after RSV infection/exposure.

We analyzed 1,019 sera from 422 individuals in 173 households, collected 365 days before and after RSV infection or exposure (2014-2022), from a longitudinal cohort with active respiratory infection surveillance. IgG against RSV pre-F was measured by electrochemiluminescence assay. We used a Cox model, adjusted for age, to assess the association between log₄ pre-infection/exposure IgG and risk of RT-PCR-confirmed infection. We compared pre- to post-infection/exposure IgG geometric mean concentration (GMC) increases among cases and household contacts to identify asymptomatic infections. Generalized additive mixed models predicted IgG concentrations over time.

We identified 113 confirmed RSV cases and 377 exposed household contacts. Cases had significantly lower pre-F IgG before infection (p<0.05) and significantly higher levels after infection (p<0.05). A one-unit increase in log4 pre-infection IgG decreased the risk of infection by 25% (p<0.05). Among 58 cases with pre- to post-RSV GMC increases, the mean fold increase was 1.12. Eight individuals without confirmed infections had ≥1.12 fold increases and were classified as probable asymptomatic infections. Cases had the highest IgG concentrations after infection, peaking at one month (p<0.001).

Pre-F IgG is a reliable CoP for RSV infection risk. We found that RSV pre-F IgG mediated protection starts to wane 6 months after infection. Therefore, scheduling of RSV vaccination should be evaluated so individuals with the highest risk of severe disease are protected throughout RSV season.